Rheumatoid Arthritis (RA) is a complex polygenic disorder. On the basis of twin and family studies, it is likely that anywhere from three to ten different genes may be involved in this disease. Only one of these genetic regions, located in the HLA complex on chromosome 6, has been defined. A major challenge for researchers is to identify the remaining regions which are involved in predisposition to RA. The purpose of this contract is to identify 1000 families in which two or more siblings are affected with rheumatoid arthritis. Detailed clinical information on affected siblings will be obtained and entered into a database. In addition, hand x-rays, serum and peripheral blood DNA will be obtained from each affected sibling. DNA will also be obtained from the parents of these siblings, when available. This database, serum and DNA repository will form a resource for the entire scientific community to allow for a comprehensive analysis of genetic susceptibility to rheumatoid arthritis. Access to the database and DNA repository by qualified scientists will be governed by an oversight committee. PROGRESS TO DATE: Study enrollment began in November 1997 with a projected endpoint of July 31, 1999. Twenty eight families have been enrolled including 48 females and 16 males. Two families were withdrawn from the study because only one sibling was found to meet study criteria. Study visits have been completed for 16 families with 13 visits completed on the GCRC. Subjects have been recruited by physicians at DUMC and VA Medical Center in Durham, by notifying the Duke Affiliated Rheumatology Trials Consortium (DART) members, mailings to Rheumatologists in North Carolina, South Carolina and Florida requesting patient referrals, and participation in a national toll-free information line for prospective participants. The advertising campaign includes advertisements in Athritis Today, the National Arthritis Foundation Magazine and additional publicity provided by the National Institutes of Health. There are no preliminary results to date. SIGNIFICANCE: This study will help elucidate the genetic causes of rheumatoid arthritis. In addition, the following resources will be available at the conclusion of the study: a) family trees from at least 1000 families with two or more sibs with RA, without personal identifiers and b) DNA samples from affected sib pairs and their parents (when available).